Oral vaccination of monkeys with an invasive Escherichia coli K-12 hybrid expressing Shigella flexneri 2a somatic antigen

Abstract

A living oral vaccine, designed to protect against Shigella flexneri 2a infections, was constructed by using Escherichia coli K-12 as a carrier strain. The hybrid strain, designated EC104, contained both chromosomal and plasmid genes from S. flexneri donor strains, In addition to expressing the S. flexneri 2a somatic antigen, it had inherited the property of epithelial-celi invasion. After the oral administration to rhesus monkeys, EC104 was isolated from the feces for up to 3 days, but by day 4 all stool cultures were negative. The serum antibody response against S. flexneri 2a somatic antigen was variable, but the vaccine conferred significant protection against an oral challenge with virulent S. flexneri 2a.

Immunoprotective oral whole cell vaccine for enterotoxigenic Escherichia coli diarrhea prepared by in situ destruction of chromosomal and plasmid DNA with colicin E2

“…We prefer to believe that protection was the result of simultaneous exposure to the several ETEC virulence factors in a train of events consistent with those which take place during natural infection. This concept, which might be termed multifactorial immunoprotection, is consistent with results reported with animal models [32,33] and also vaccine trials employing volunteers [9][10][11]14,30] indicating promising results with vaccine preparations containing more than one virulence factor, in some cases including somatic antigen.…”

“…Various strategies have been employed in attempts to develop vaccines against bacterial enteropathogens such as Shigella, Salmonella, V. cholerae and ETEC, and various degrees of success have been achieved. The approaches differ primarily in the form of antigen chosen for oral administration; i.e., living attenuated strains [5,[9][10][11], whole bacteria killed by either heat and/or chemicals [28,29], purified toxoids to provoke anti-toxin immunity [7,13,14] and purified fimbrial CFAs to provoke immunity against intestinal colonization [12,[16][17]. Candidate vaccines have been designed for each pathogen mainly on the basis of recognized mechanisms of pathogenesis, antigenicity of killed cell preparations or purified virulence factors, and in consideration of the risk of minor but undesirable responses to living attenuated strains.…”

“…Two major approaches have been used in vaccine development to prevent diarrheal disease produced by V. cholerae, Salmonella, and ETEC. Both approaches are aimed at oral administration of antigens, either in the form of live attenuated bacterial strains [9][10][11] or of non-replicating macromolecules responsible for virulence, so-called virulence factors [12 17]. Both of these approaches have given promising results, although attenuated strains have a tendency to cause mild diarrhea in some vaccinees.…”

Shigella flexneri infection: a histopathologic study of colonic biopsies in monkeys infected with virulent and attenuated bacterial strains

“…Formal, WRAIR, Washington DC., USA) is a S. flexneri serotype 2a strain, previously proven virulent in monkeys (4,5).…”

Potentials of Shigella flexneri Y strain TSF21 as a candidate vaccine against shigellosis: safety, immunogenicity and protective efficacy in Bonnet monkeys

“…On the other hand, invasive hybrid derivatives (E. coli bearing somatic antigens of Shigella) were protective in monkeys [4]. In an efficacy trial in monkeys 169 with another hybrid vaccine which was Serenynegative but invaded HeLa cells, mild mucosal inflammation (suggestive of invasion) was detected and the vaccine provided significant protection [6]. Invasive ability of a live vaccine thus appears to be critical for a protective immune response.…”